Evaluation of Prostate HistoScanning as a Method for Targeted Biopsy in Routine Practice.

BACKGROUND: Prostate HistoScanning (PHS) is a tissue characterization system used to enhance prostate cancer (PCa) detection via transrectal ultrasound imaging. OBJECTIVE: To assess the impact of supplementing systematic transrectal biopsy with up to three PHS true targeting (TT) guided biopsies on the PCa detection rate and preclinical patient assessment. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective study involving a cohort of 611 consecutive patients referred for transrectal prostate biopsy following suspicion of PCa. PHS-TT guided cores were obtained from up to three PHS lesions of ≥0.5cm3 per prostate and only one core per single PHS lesion. Histological outcomes from a systematic extended 12-core biopsy (Bx) scheme and additional PHS-TT guided cores were compared. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Comparison of PHS results and histopathology was performed per sextant. The χ2 and Mann-Whitney test were used to assess differences. Statistical significance was set at p<0.05. RESULTS AND LIMITATIONS: PHS showed lesions of ≥0.5cm3 in 312 out of the 611 patients recruited. In this group, Bx detected PCa in 59% (185/312) and PHS-TT in 87% (270/312; p<0.001). The detection rate was 25% (944/3744 cores) for Bx and 68% (387/573 cores) for PHS-TT (p<0.001). Preclinical assessment was significantly better when using PHS-TT: Bx found 18.6% (58/312) and 8.3% (26/312), while PHS-TT found 42.3% (132/312) and 20.8% (65/312) of Gleason 7 and 8 cases, respectively (p<0.001). PHS-TT attributed Gleason score 6 to fewer patients (23.4%, 73/312) than Bx did (32.4%, 101/312; p=0.0021). CONCLUSIONS: Patients with a suspicion of PCa may benefit from addition of a few PHS-TT cores to the standard Bx workflow. PATIENT SUMMARY: Targeted biopsies of the prostate are proving to be equivalent to or better than standard systematic random sampling in many studies. Our study results support supplementing the standard schematic transrectal ultrasound-guided biopsy with a few guided cores harvested using the ultrasound-based prostate HistoScanning true targeting approach in cases for which multiparametric magnetic resonance imaging is not available.

Beam distortion due to gold fiducial markers during salvage high-intensity focused ultrasound in the prostate.

PURPOSE: High intensity focused ultrasound (HIFU) provides a non-invasive salvage treatment option for patients with recurrence after external beam radiation therapy (EBRT). As part of EBRT the prostate is frequently implanted with permanent fiducial markers. To date, the impact of these markers on subsequent HIFU treatment is unknown. The objective of this work was to systematically investigate, using computational simulations, how these fiducial markers affect the delivery of HIFU treatment. METHODS: A series of simulations was performed modelling the propagation of ultrasound pressure waves in the prostate with a single spherical or cylindrical gold marker at different positions and orientations. For each marker configuration, a set of metrics (spatial-peak temporal-average intensity, focus shift, focal volume) was evaluated to quantify the distortion introduced at the focus. An analytical model was also developed describing the marker effect on the intensity at the focus. The model was used to examine the marker's impact in a clinical setting through case studies. RESULTS: The simulations show that the presence of the marker in the pre-focal region causes reflections which induce a decrease in the focal intensity and focal volume, and a shift of the maximum pressure point away from the transducer's focus. These effects depend on the shape and orientation of the marker and become more pronounced as its distance from the transducer's focus decreases, with the distortion introduced by the marker greatly increasing when placed within 5 mm of the focus. The analytical model approximates the marker's effect and can be used as an alternative method to the computationally intensive and time consuming simulations for quickly estimating the intensity at the focus. A retrospective review of a small patient cohort selected for focal HIFU after failed EBRT indicates that the presence of the marker may affect HIFU treatment delivery. CONCLUSIONS: The distortion introduced by the marker to the HIFU beam when positioned close to the focus may result in an undertreated region beyond the marker due to less energy arriving at the focus, and an overtreated region due to reflections. Further work is necessary to investigate whether the results presented here justify the revision of the patient selection criteria or the markers' placement protocol.

MRI-targeted prostate biopsy: a review of technique and results.

Multiparametric magnetic resonance imaging (mpMRI) is of interest for the diagnosis of clinically significant prostate cancer and mpMRI-targeted biopsies are being used increasingly in clinical practice. Target acquisition is performed using a range of magnet strengths and varying combinations of anatomical and functional sequences. Target identification at the time of biopsy can be carried out in the MRI scanner (in-bore biopsy) or, more commonly, the MRI-target is biopsied under ultrasonographic guidance. Many groups use cognitive or visual registration, whereby the biopsy target is identified on MRI and ultrasonography is subsequently used to direct the needle to the same location. Other groups use registration software to show prebiopsy MRI data on real-time ultrasonography. The reporting of histological results in MRI-targeted biopsy studies varies greatly. The most useful reports compare the detection of clinically significant disease in standard cores versus mpMRI-targeted cores in the same cohort of men, as recommended by the STAndards of Reporting for MRI-Targeted biopsy studies (START) consensus panel. Further evidence is needed before an mpMRI-targeted strategy can be recommended as the standard intervention for men at risk of prostate cancer.

Is an extended 20-core prostate biopsy protocol more efficient than the standard 12-core? A randomized multicenter trial.

PURPOSE: We determined the impact of increasing the number of cores from 12 to 20 at initial prostate biopsy in men suspicious of prostate cancer. MATERIALS AND METHODS: From December 2009 to November 2011, patients in 7 centers scheduled for a first prostate biopsy, with a prostate specific antigen less than 20 ng/ml and no nodule on digital rectal examination, were invited to participate in this superiority trial. Patients were randomized to a 12-core (PB12 group) or a 20-core (PB20 group) protocol. The primary end point was cancer detection rate. Secondary end points were cancer characteristics, rate of complications and patient tolerance assessed by a self-completed booklet before prostate biopsy and at day 5 and day 15. RESULTS: A total of 339 patients were randomized. Preoperative variables were similar in both groups. Cancer was detected in 71 patients (42.0%) in PB12 group and in 81 patients (48.8%) in PB20 group, and the difference was not significant (p >0.2). Gleason score and cancer length measured on prostate biopsy cores were not significantly different between groups. Although the cancer detection rate was linked to prostate volume, this was not affected by the number of extracted cores (p >0.4). Complications number and seriousness were comparable in both arms. No significant difference was noted regarding side effects and tolerance as self-assessed by the patient at day 5 and day 15 after prostate biopsy. CONCLUSIONS: Our findings suggest that there is no significant advantage in using a 20-core biopsy protocol vs 12-core protocol during an initial prostate biopsy.

Ultrasonidos Focalizados de Alta Energía (HIFU) de Rescate en el cáncer de próstata después de Radioterapia / Salvage High energy focalized ultrasound (HIFU) in prostate cancer after radiotherapy

OBJETIVO: Evaluar la eficacia y seguridad de los Ultrasonidos de Alta Intensidad Focalizados (HIFU) como tratamiento de rescate tras radioterapia radical en el cáncer de próstata (CP). MÉTODOS: Se revisa la literatura a través de bases de datos y los artículos publicados que hacen referencia a este tratamiento entre el año 2000 y el 2010. Se han evaluado los resultados oncológicos, así como los efectos adversos, comparando con lo publicado en relación con otras terapias existentes. RESULTADOS: Se evalúan las distintas series publicadas, en las que se incluyen los resultados de los dos dispositivos disponibles en la actualidad, todas ellas con sus resultados iniciales y las que se encuentran en fase de ajuste de dosis. Se puede afirmar de forma general que el mayor problema de todas ellas resulta la morbilidad incial que se reduce según se gana en experiencia con el tratamiento. De forma generalizada, hay que resaltar la importancia de lo cortas que son las series evaluadas, sobre todo en tiempo de seguimiento y en número de pacientes. Asimismo, salvo una revisión sistemática recientemente publicada, no existe ningún estudio prospectivo con ninguno de los dos dispositivos. Todos los resultados de las distintas series publicadas son comparados con la literatura existente en relación a los distintos tratamientos del CP. CONCLUSIONES: A pesar de los resultados publicados, el tratamiento mediante HIFU en la recidiva del cáncer de próstata tras radioterapia es una opción que debe ser considerada. Sobre todo teniendo en cuenta que, en estos pacientes, es importante retrasar el desarrollo de la enfermedad y que no existen otras alternativas que hayan demostrado ser eficaces. Es necesaria una mayor investigación para explorar la utilización de HIFU en el tratamiento cel CP. En cualquier caso, es fundamental la publicación de series prospectivas comparativas y series con mayor número de pacientes y de más largo seguimiento para poder sacar conclusiones definitivas(AU)

OBJECTIVES: To evaluate the efficacy and safety of High Intensity Focused Ultrasound (HIFU) as salvage treatment after radical radiotherapy in prostate cancer (PC). METHODS: We reviewed the literature through databases and published articles that refer to this treatment between 2000 and 2010. We evaluated oncological results and adverse effects, compared with those published in conjunction with other therapies. RESULTS: We evaluated the different series, which include the results of the two devices currently available, all with their initial results and those that are in the process of dose adjustment. Generally, it can be said that the biggest problem of all is that initial morbidity is reduced as the surgeon gains experience with the treatment. We must stress the importance of the short series that are evaluated, especially in follow-up time and number of patients. Also, except for a recently published systematic review, no prospective studies are published. The results from different series are compared with existing literature regarding to other PC treatments. CONCLUSIONS: In spite of published results, the treatment with HIFU for prostate cancer recurrence after radiotherapy is an option that should be considered. Especially considering that, it is important to delay the development of the disease in these patients, and there are no other alternatives that have proven to be effective. Further research is needed to explore the use of HIFU in the treatment of PC. Anyway, it is essential to publish comparative prospective series and series with more patients and longer follow-up to draw definitive conclusions(AU)

High-intensity focused ultrasound for localized prostate cancer: initial experience with a 2-year follow-up.

OBJECTIVE: To report on the short-term functional and oncological results, from one institution, of high-intensity focused ultrasound (HIFU) for treating localized prostate cancer. PATIENTS AND METHODS: Over a 3-year period, 43 patients with localized prostate cancer were scheduled for HIFU in the primary (31) and salvage (12) settings using a second-generation Ablatherm device (EDAP, Lyon, France). Oncological failure was defined by several criteria, including biochemical failure (assessed using both the Phoenix definition of the nadir + 2 ng/mL) and the current Food and Drug Administration (FDA) trial endpoint of a prostate-specific antigen (PSA) level of > or = 0.5 ng/mL, or starting salvage therapy, or the presence of cancer on biopsy after treatment. RESULTS: Three patients had their procedures abandoned due to technical limitations/rectal wall thickness. The mean PSA levels in the primary and salvage groups were 9.2 and 5.1 ng/mL, respectively. The mean HIFU treatment time in the primary and salvage groups was 71.1 and 63.3 min, respectively. Using the Phoenix definition of biochemical failure, HIFU treatment failed in 13 patients in the primary group (46%) and five in the salvage group. Using the FDA trial endpoint, HIFU failed in 21 patients in the primary group (75%) and eight in the salvage group. One man died from metastatic prostate cancer 18 months after salvage HIFU. There were two urethral strictures in the primary (7%) and one in the salvage treatment group. There were two prostato-rectal fistulae in the salvage HIFU group. CONCLUSIONS: HIFU is proposed to be a minimally invasive low-morbidity ablative treatment for localized prostate cancer, and with good efficacy. The present limited series is unable to support these claims. There were significant rates of complications and oncological failure in both the primary and salvage setting. As a result we have suspended our programme pending further evidence of its safety and efficacy.

The feasibility and safety of high-intensity focused ultrasound as salvage therapy for recurrent prostate cancer following external beam radiotherapy.

OBJECTIVES: To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT). PATIENTS AND METHODS: A review of 31 cases treated using the Sonablate 500 HIFU device, between 1 February 2005 and 15 May 2007, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following EBRT. RESULTS: The mean (range) age was 65 (57-80) years with a mean preoperative PSA level of 7.73 (0.20-20) ng/mL. The patients were followed for a mean (range) of 7.4 (3-24) months. Side-effects included stricture or intervention for necrotic tissue in 11 of the 31 patients (36%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in two (7%). Recto-urethral fistula occurred in two men, although one was due to patient movement due to inadequate anaesthesia, so the 'true' rate is 3%. Half of the patients had PSA levels of <0.2 ng/mL at the last follow-up. Three patients had metastatic disease whilst another two had only local, histologically confirmed, failure. A further four patients had evidence of biochemical failure only. Overall, 71% had no evidence of disease following salvage HIFU. CONCLUSIONS: Salvage HIFU is a minimally invasive daycase procedure that can achieve low PSA nadirs and good cancer control in the short term, with comparable morbidity to other forms of salvage treatment. The issue of accurate staging at the time of recurrence is still problematic, as a proportion of these men will harbour microscopic metastases undetected by conventional staging investigations.

[Optimal evaluation of the infertile male. 2007 French urological association guidelines]. / Evaluation de l'homme infertile: recommandations AFU 2007.

An infertility evaluation should be performed if a couple has not achieved conception after one year of unprotected intercourse. An evaluation should be performed earlier if male or female infertility risk factors exist and if the couple questions its fertility potential. The initial screening of the male should include a reproductive history and a physical examination performed by a urologist or a specialist in male fertility and two semen analyses. Additional procedures and testing may be used to elucidate problems discovered during the full evaluation. The minimal initial endocrine evaluation should include serum total testosterone and serum follicle-stimulating hormone levels. An endocrine evaluation should be performed if sperm concentration is abnormally low, sexual function is impaired, and when other clinical findings suggest a specific endocrinopathy. A postejaculatory urinalysis should be performed if ejaculate volume is less than 1 mL, except in patients with bilateral vasal agenesis or possible hypogonadism. With a diagnosis of retrograde ejaculation, specific management should be considered before advising assisted reproductive technology. Scrotal ultrasonography is indicated when physical examination of the scrotum is difficult or inadequate, or when a testicular mass is suspected. Transrectal ultrasonography (TRUS) is indicated in patients who are azoospermic or have a low ejaculate volume. Specialized testing of semen is not required for routine diagnosis of male infertility. However, some tests may be useful for a few patients to identify a male factor contributing to unexplained infertility, or to select therapy (e.g., assisted reproductive technology). Before performing intracytoplasmic sperm injection, karyotyping and Y-chromosome analysis should be offered to men who have nonobstructive azoospermia and severe oligospermia. Genetic testing for gene mutations of the ABCC7 (ex-CFTR) gene should be offered to male and female partners before proceeding with treatments that use the sperm of men with congenital bilateral absence of the vasa deferentia or congenital unilateral abnormality of the seminal tract. Genetic counseling may be offered when a genetic abnormality is suspected in the male or female partner, and it should be provided when a genetic abnormality is detected. Genetic testing in the female partner, when non symptomatic, should only be advised by a physician from a multidisciplinary team registered by the ministry of health. Evaluation by testis biopsy and deferentography should be performed by a urologist or an andrologist registered for sperm retrieval.

Significance of suspicious lesions at transrectal ultrasonography in men with serum prostate-specific antigen levels of < 20 ng/ml.

AIMS AND BACKGROUND: The objective of the study was to evaluate the significance of suspicious lesions at transrectal ultrasonography for prostate cancer diagnosis. PATIENTS AND METHODS: A total of 1,009 men with a mean age of 65.0 +/- 7.7 years (range, 40.0-79.0) constituted the study cohort and 265 (26.3%) were diagnosed with prostate cancer on initial biopsy. RESULTS: The cancer detection rate was higher in patients with suspicious lesions (33.2%) than in those with no suspicious lesion (21.5%) (P < 0.001). Pathologic findings of the needle biopsy samples also showed more aggressive characteristics in men with suspicious lesions (P < 0.05). Of 413 men with suspicious lesions, additional lesion-directed biopsies were performed in 133 patients. The positive predictive value of additional lesion-directed biopsy was 18.0%. Of patients who had positive cores on lesion-directed biopsies, all were also found to have positive cores on random biopsies, and no patient had positive cores only on lesion-directed biopsies. The Gleason score was not changed by the findings of lesion-directed biopsies in these patients. CONCLUSIONS: Our findings do not provide a rationale to recommend the addition of lesion-directed biopsy in patients with suspicious lesions at transrectal ultrasonography. However, men with suspicious lesions at transrectal ultrasonography had a higher risk of being diagnosed with prostate cancer.

Visually directed high-intensity focused ultrasound for organ-confined prostate cancer: A proposed standard for the conduct of therapy.

OBJECTIVE: To propose a standard for the conduct of visually directed transrectal high-intensity focused ultrasound (HIFU) and to offer a formal description of the changes observed on B-mode ultrasonography (US) during this procedure. We describe our early experience of using two different treatment methods; algorithm-based HIFU and visually directed HIFU for the treatment of organ-confined prostate cancer. PATIENTS AND METHODS: Between November 2004 and October 2005, 34 men were treated using the Sonablate-500 (Focus Surgery, Indianapolis, IN, USA) as primary therapy for T1 or T2 prostate cancer. None had had previous hormone therapy and all had > or = 3-month PSA nadirs recorded at the follow-up. Nine men were treated using an algorithm-based protocol (group 1) and 25 using visually directed therapy (group 2). The conduct of visually directed treatment was described and changes seen using B-mode US were categorized using three 'Uchida' grades. RESULTS The mean PSA nadir achieved in group 2 was 0.15 ng/mL, vs 1.51 ng/mL in group 1 (P < 0.005). In group 2, 21 of 25 men achieved PSA nadirs of < or = 0.2 ng/mL 3 months after treatment. Seven men achieved undetectable PSA values. The occurrence rate of treatment-related toxicity was similar in both groups. CONCLUSION: Visually directed, transrectal HIFU enables clinically important and statistically significantly lower PSA nadirs to be achieved than algorithm-based HIFU. This is the first reported experience of visually directed HIFU for the treatment of organ-confined prostate cancer. We think that this is the first attempt to standardize the conduct of therapy; such standardization facilitates teaching it, and makes it possible to derive quality standards. The standardization of the conduct of therapy is a key step in the process of health technology assessment.

[Evaluation of ultrasonography effectiveness in prostate cancer detection].

The database of examining 624 patients aged 49-85 were analyzed to define the diagnostic effectiveness of gray-scale, color and power Doppler transrectal ultrasonography (TRUS). Among them there are 473 (75.8%) cancer patients and 151 (24.2%) benign prostate diseases patients. All the patients underwent a transrectal ultrasound examination with multifocal biopsy. The gray-scale, color and power Doppler transrectal ultrasound examination has the diagnostic accuracy of 75,3%. At this the effectiveness of the method increases with the Gleason sum growing.